Asthma is the most common chronic disease in industrialized nations, affecting >10 million people in the U.S. alone. Familial aggregation and concordance rates in monozygotic twins have suggested a genetic component to asthma, but elucidating the role of specific genes using traditional approaches has been challenging. We hypothesize that immunologic programming in the fetus results from the interplay between fetal genotype and the environmental challenges of pregnancy, which is influenced by both maternal genotype and her environmental exposures, and that such programming influences subsequent response to viral infections and risk for asthma and atopic disease. Our investigations will be conducted in families participating in the prospective COAST (Childhood Onset of Asthma) Study. We will genotype the COAST child and both parents for variation in 1) 16 genes that encode cytokines, chemokines, and their receptors, that have been implicated in asthma pathogenesis; 2) genes identified through positional cloning studies of asthma or atopy genes; and 3) two HLA class II genes that likely influence the overall immunologic milieu during pregnancy. Main effects of and interactions between genotypes and haplotypes at each locus on the following phenotypes will be assessed during the first 6 years of life: 1) cytokine responses in cord blood and in peripheral blood collected at yearly intervals; 2) cytokine levels in nasopharyngeal mucus specimens collected during RSV infection; 3) persistent wheezing after RSV infection and late-onset wheezing; 4) allergic sensitization; 5) development of atopic dermatitis, allergic rhinitis, and asthma; and 6) airway physiology. In addition, we will evaluate associations between maternal-fetal HLA compatibility and exacerbation of asthma symptoms during pregnancy in mothers with asthma. These studies have the potential to identify novel interactions that influence asthma pathogenesis. Thereby allowing for the development of new therapies and intervention strategies for these common diseases.